The Incidence of Infective Endocarditis in
England is Increasing
An Assessment of the Impact of Cessation of
Antibiotic Prophylaxis Using Population
Statistics
Dr Mark Dayer, Taunton and Somerset NHS Trust, UK
Professor Simon Jones, University of Surrey, UK
Dr Bernard Prendergast, John Radcliffe Hospital, UK
Professor Larry Baddour, Mayo Clinic, USA
Professor Peter Lockhart, Carolinas Medical Centre, USA
Professor Martin Thornhill, University of Sheffield, UK
Invasive dental
procedure
Viridans
streptococci
released into
circulation
IE develops in
susceptible
individuals
Antibiotic
Prophylaxis
(AP)
Invasive
dental
procedure
Circulating
viridans
streptococci
reduced
Presumed
reduced risk
of IE
Historical Perspective
• 1955: First AHA Guidelines on AP
• Successive guidelines have tended to
recommend:
– Smaller doses of antibiotics given for a shorter time
– That fewer patients regarded as being at risk of IE
– Fewer invasive procedures covered
• Increasing controversy over time
• No randomized trial of AP
UK NICE Guidelines: March
2008
NICE - March 2008
1.1.3 Antibiotic prophylaxis against infective
endocarditis is not recommended:
• For people undergoing dental procedures
• For people undergoing non-dental procedures
at the following sites:
– Upper and lower gastrointestinal tract
– Genitourinary tract
– Upper and lower respiratory tract
Funded opportunity to study the
impact of stopping antibiotic
prophylaxis at a national level
Methodology
• England only - ~ 50m
• All prescriptions for single doses of
amoxicillin 3g or clindamycin 600mg
• Jan 1st 2004 – March 31st 2013
• Patients discharged from English
hospitals with a primary diagnosis of
infective endocarditis
• Jan 1st 2000 – March 31st 2013
• Superspells
• 19,804 cases in total
Number of Prescriptions of Amoxicillin 3g or
Clindamycin 600mg
Antibiotic Prophylaxis Prescribing Data
NICE
guidelines
Average pre:
Average final 6m:
Reduction:
10,900
1,307
88%, p<0.001
Incidence of Infective Endocarditis Cases
(Superspells) and Deaths / 10 Million / Month
Incidence of IE
Incidence of Infective Endocarditis Cases
(Superspells) and Deaths / 10 Million / Month
Incidence of IE
Incidence of Infective Endocarditis Cases
(Superspells) and Deaths / 10 Million / Month
Incidence of IE
After NICE there was a significant
increase in the number of IE cases/month
above the previous trend
(0.11 cases/10 million/month, CI 0.050.16, p<0.0001)
By March 2013 this
amounted to an extra:
• 35 IE cases/month
Incidence of Infective Endocarditis Cases
(Superspells) / 10 Million / Month
Change Point Analysis
Change Point June 2008
Incidence of Infective Endocarditis Cases
(Superspells) and Deaths / 10 Million / Month
In-Patient Mortality
A potential, but not
significant, extra:
• 1.5 IE deaths/month or
• 18 IE deaths/year
Incidence of Infective Endocarditis Cases
(Superspells) / 10 Million / Month
Highest and Lower Risk
Conclusions
• Five years post NICE there has been:
– a large and significant fall in AP prescribing
– a significant increase in the incidence of IE
• Individuals affected include highest risk and lower
risk individuals
• Although there is a temporal association, we
cannot conclude there is a cause-effect
relationship
• Need for a prospective RCT
In Addition
NICE have issued a press release to say that
they will undertake an immediate review of their
guidance.
There are no recommendations for a change in
practice at present.
The study has just been published by the
Lancet:
http://dx.doi.org/10.1016/S0140-6736(14)62007-9
Funding
Heart Research-UK & Simplyhealth
grant (Ref: RG2632/13/14)
NIH/NIDCR grant (Ref:
1R03DE023092-01)